New Research Findings

Two recent studies published in JAMA: the Journal of the American Medical Association, focused on vaccines administered to infants. Although the intussusception risk previously attributed to the pentavalent rotavirus vaccine was shown to be negligible in one of the studies, a limited increased risk of febrile seizures was seen with administration of an acellular pertussis-containing combination vaccine in the other.

Pentavalent Rotavirus Vaccine

The pentavalent rotavirus vaccine does not pose an increased risk of intussusception when administered to infants, according to a study(jama.ama-assn.org) published Feb. 8 in JAMA.

The study report, "Risk of Intussusception Following Administration of a Pentavalent Rotavirus Vaccine in U.S. Infants," looked at the outcomes of nearly 800,000 doses of the vaccine administered in the United States from May 2006 through February 2010, with more than one-third of those being first doses. During the course of the prospective postlicensure study, researchers did not observe any statistically significant risk and noted that an excess risk of one intussusception event per 65,287 vaccines following a first dose can reliably be excluded.

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A large prospective postmarketing study of pentavalent rotavirus vaccine and intussusception looked at nearly 800,000 vaccination outcomes, finding no significant increase in intussusception.

Two earlier international studies had suggested the possibility of an elevated intussusception risk in the first week after the first vaccine dose.

In a study of Danish children, a combination vaccine containing an acellular pertussis component was associated with an increased risk of febrile seizures, but only on the day of participants' 3-month and 5-month vaccinations.

The Danish study also showed that the absolute risk of febrile seizures is small and that the acellular pertussis-containing vaccine was not associated with epilepsy.

"Among U.S. infants aged 4 to 34 weeks who received (the pentavalent rotavirus vaccine), the risk of intussusception was not increased compared with infants who did not receive the rotavirus vaccine," the researchers said. "The introduction of rotavirus vaccines has had a substantial public health effect on severe rotavirus disease in U.S. infants. Although we cannot entirely exclude the possibility of a very low-level risk, the findings of our study strengthen the evidence base in favor of vaccination for effective control of severe childhood rotavirus disease."

The study comes on the heels of two recent postlicensure evaluations of rotavirus vaccine: one from Australia that involved the pentavalent vaccine and one from Mexico and Brazil that involved monovalent vaccine. Each study suggested the possibility of an elevated risk in the first week after the first vaccine dose.

"Because of the new data on intussusception risk from international settings and the almost four-fold increase in rotavirus vaccine doses administered in the Vaccine Safety Datalink (VSD) population since the previous analysis (i.e., a postlicensure study of the pentavalent vaccine in 2008), we reexamined intussusception risk associated with rotavirus vaccination in the VSD population, with a specific focus on the one- to seven-day risk window after dose one administration," the researchers said.

The researchers concluded that the known benefits of rotavirus vaccination in the United States outweigh any potential low-level risk for intussusception that might exist.

"These findings are especially important given that rotavirus vaccine coverage in the U.S. has steadily increased since its introduction and averaged 72 percent in June 2009 among 5-month-olds selected from eight different sentinel sites across the country," they said.

The population-based cohort study, which was reported in the Feb. 22/29 issue of JAMA, involved 378,834 children born in Denmark between Jan. 1, 2003, and Dec. 31, 2008. Among that population, 329,521 (87.0 percent) were exposed to the first DTaP-IPV-Hib vaccination, 339,288 (90 percent) to the second, and 320,049 (84.5 percent) to the third during follow-up.

Data showed that, although the absolute danger is small, DTaP-IPV-Hib vaccination at ages 3 and 5 months is associated with an increased risk of febrile seizures on the day of vaccination. No such increased risk was associated with the third dose, which study participants received at age 12 months.

"Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the three vaccinations versus a reference cohort of children who were not within 0 to 7 days of vaccination," the researchers said. "However, a higher risk of febrile seizures was found on the day of the first and on the day of the second, but not on the day of the third, vaccination versus the reference cohort."

The researchers further noted that the risks of recurrent febrile seizures or subsequent epilepsy were not increased for children who had their first febrile seizure within seven days of vaccination. In addition, the risk of epilepsy was not higher among vaccinated versus unvaccinated children.

"It is unclear why the (hazard ratios) of febrile seizure increased only after the first two vaccinations, but not after the third vaccination, when the underlying incidence of febrile seizures was higher," the researchers said. "There may be more competing risk factors for febrile seizures during a period in which the incidence of febrile seizures is high and the relative importance of a single risk factor like vaccination may be lower."

The researchers acknowledged that because the DTaP-IPV-Hib vaccine was given as a combined vaccine throughout the study period, some uncertainty remains as to which of the vaccine components caused febrile seizures on the day of vaccination. Previous studies, however, have shown that the DTaP vaccine displays a pattern of adverse events similar to that of diphtheria and tetanus vaccine without the acellular pertussis component.